The purpose of this study was to examine the effects of exercise on cardiovascular disease (CVD) risk factors in children and adolescents with obesity. Randomized controlled trials (RCTs) of exercise ≥4 weeks in children and adolescents with obesity were included if one or more CVD risk factors were included as an outcome. Studies were retrieved by searching 7 electronic databases, cross-referencing, and expert review. Data were pooled using the inverse-variance heterogeneity (IVhet) model and strength of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. Thirty-nine studies representing 1548 participants (847 exercise, 701 control) met the inclusion criteria. Aerobic exercise improved 10 of 12 (83.3%) outcomes ( < .05 for all) while combined aerobic and strength training improved 5 of 8 (62.5%) outcomes ( < .05 for all). The strength of evidence ranged from "very low" to "moderate." It was concluded that aerobic exercise, as well as combined aerobic and strength training, is associated with improvements in multiple CVD risk factors among children and adolescents with obesity. However, the generally low strength of evidence suggests a need for future well-designed and conducted RCTs on the effects of exercise, especially strength training, in children and adolescents with obesity.